rs4963051

chr11-1243735-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002458.3(MUC5B):c.6855G>A(p.Thr2285=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,602,934 control chromosomes in the GnomAD database, including 24,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2030 hom., cov: 30)
  • Exomes 𝑓: 0.17 (22961 hom.)
• Consequence: MUC5B NM_002458.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.76

Genes affected

MUC5B (HGNC:7516): (mucin 5B, oligomeric mucus/gel-forming) This gene encodes a member of the mucin family of proteins, which are highly glycosylated macromolecular components of mucus secretions. This family member is the major gel-forming mucin in mucus. It is a major contributor to the lubricating and viscoelastic properties of whole saliva, normal lung mucus and cervical mucus. This gene has been found to be up-regulated in some human diseases, including sinus mucosa of chronic rhinosinusitis (CRS), CRS with nasal polyposis, chronic obstructive pulmonary disease (COPD) and H. pylori-associated gastric disease, and it may be involved in the pathogenesis of these diseases. [provided by RefSeq, Jul 2010]

MUC5B-AS1 (HGNC:53936): (MUC5B antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-1243735-G-A is Benign according to our data. Variant chr11-1243735-G-A is described in ClinVar as [Benign]. Clinvar id is 403142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.76 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MUC5B	NM_002458.3	c.6855G>A	p.Thr2285=	synonymous_variant	31/49	ENST00000529681.5
MUC5B-AS1	NR_157183.1	n.57-1097C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MUC5B	ENST00000529681.5	c.6855G>A	p.Thr2285=	synonymous_variant	31/49	5	NM_002458.3	P1
MUC5B-AS1	ENST00000532061.2	n.57-1097C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24270 AN: 151428 Hom.: 2028 Cov.: 30

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.00502

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.146

GnomAD3 exomes AF: 0.146 AC: 36308 AN: 248502 Hom.: 3184 AF XY: 0.151 AC XY: 20356 AN XY: 134878

Gnomad AFR exome AF: 0.155

Gnomad AMR exome AF: 0.0814

Gnomad ASJ exome AF: 0.149

Gnomad EAS exome AF: 0.00317

Gnomad SAS exome AF: 0.149

Gnomad FIN exome AF: 0.201

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.151

GnomAD4 exome AF: 0.170 AC: 246445 AN: 1451388 Hom.: 22961 Cov.: 146 AF XY: 0.170 AC XY: 122542 AN XY: 722370

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.0857

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.00209

Gnomad4 SAS exome AF: 0.147

Gnomad4 FIN exome AF: 0.193

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.160 AC: 24282 AN: 151546 Hom.: 2030 Cov.: 30 AF XY: 0.159 AC XY: 11773 AN XY: 74036

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.00503

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.147

Alfa AF: 0.169 Hom.: 717

Bravo AF: 0.151

EpiCase AF: 0.172

EpiControl AF: 0.173

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.3
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4963051; hg19: chr11-1264965; COSMIC: COSV71589888; COSMIC: COSV71589888;